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Neuron. 2019 May 8;102(3):564-573.e6. doi: 10.1016/j.neuron.2019.02.029. Epub 2019 Mar 13.

Pain-Induced Negative Affect Is Mediated via Recruitment of The Nucleus Accumbens Kappa Opioid System.

Author information

1
Department of Anesthesiology, Washington University Pain Center, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA.
2
Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, Valencia 46100, Spain.
3
Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA 90095, USA.
4
Department of Anesthesiology, Washington University Pain Center, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA; Department of Pharmaceutical and Administrative Sciences, St. Louis College of Pharmacy, St. Louis, MO 63110, USA; Center for Clinical Pharmacology, St. Louis College of Pharmacy and Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA.
5
Department of Psychology, Washington State University, Pullman, WA 99164-4820, USA.
6
Department of Radiology, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA.
7
Department of Brain and Cognitive Science, Viral Gene Transfer Core, MIT, Cambridge, MA 02139-4307, USA.
8
Department of Radiology, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA; Department of Neuroscience, Washington University in St. Louis, St. Louis, MO 63110, USA.
9
Department of Anesthesiology, Washington University Pain Center, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA; Department of Neuroscience, Washington University in St. Louis, St. Louis, MO 63110, USA.
10
Department of Anesthesiology, Washington University Pain Center, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA; Department of Pharmaceutical and Administrative Sciences, St. Louis College of Pharmacy, St. Louis, MO 63110, USA; Center for Clinical Pharmacology, St. Louis College of Pharmacy and Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA. Electronic address: al-hasanir@wustl.edu.
11
Department of Anesthesiology, Washington University Pain Center, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA; Department of Neuroscience, Washington University in St. Louis, St. Louis, MO 63110, USA. Electronic address: mbruchas@uw.edu.
12
Department of Anesthesiology, Washington University Pain Center, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA; Department of Neuroscience, Washington University in St. Louis, St. Louis, MO 63110, USA. Electronic address: jmoron-concepcion@wustl.edu.

Abstract

Negative affective states affect quality of life for patients suffering from pain. These maladaptive emotional states can lead to involuntary opioid overdose and many neuropsychiatric comorbidities. Uncovering the mechanisms responsible for pain-induced negative affect is critical in addressing these comorbid outcomes. The nucleus accumbens (NAc) shell, which integrates the aversive and rewarding valence of stimuli, exhibits plastic adaptations in the presence of pain. In discrete regions of the NAc, activation of the kappa opioid receptor (KOR) decreases the reinforcing properties of rewards and induces aversive behaviors. Using complementary techniques, we report that in vivo recruitment of NAc shell dynorphin neurons, acting through KOR, is necessary and sufficient to drive pain-induced negative affect. Taken together, our results provide evidence that pain-induced adaptations in the kappa opioid system within the NAc shell represent a functional target for therapeutic intervention that could circumvent pain-induced affective disorders. VIDEO ABSTRACT.

PMID:
30878290
PMCID:
PMC6509001
[Available on 2020-05-08]
DOI:
10.1016/j.neuron.2019.02.029

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